Activation of PI3K/Akt Signaling Pathway in Rat Hypothalamus Induced by an Acute Oral Administration of D-Pinitol.

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN.

Cannabidiol prevents several of the behavioral alterations related to cocaine addiction in mice.

Cocaine dependence is a highly prevalent disease in modern society and lacks an effective treatment. Cannabidiol (CBD), a major non-psychoactive constituent of Cannabis sativa, has been shown to be a promising tool in the management of some neuropsychiatric disorders, including cocaine abuse. However, its therapeutic effects on the behavioral outcomes related to cocaine addiction remain unclear.

Can We Treat Neuroinflammation in Alzheimer's Disease?

Alzheimer's disease (AD), considered the most common type of dementia, is characterized by a progressive loss of memory, visuospatial, language and complex cognitive abilities. In addition, patients often show comorbid depression and aggressiveness. Aging is the major factor contributing to AD; however, the initial cause that triggers the disease is yet unknown.

The rewarding effects of ethanol are modulated by binge eating of a high-fat diet during adolescence.

Binge-eating is considered a specific form of overeating characterized by intermittent and high caloric food intake in a short period of time. Epidemiologic studies support a positive relation between the ingestion of fat and ethanol (EtOH), specifically among adolescent subjects. The aim of this work was to clarify the role of the compulsive, limited and intermittent intake of a high-fat food during adolescence on the rewarding effects of EtOH.

Adolescent but not adult ethanol binge drinking modulates cocaine withdrawal symptoms in mice.

Background: Ethanol (EtOH) binge drinking is an increasingly common behavior among teenagers that induces long-lasting neurobehavioral alterations in adulthood. An early history of EtOH abuse during adolescence is highly correlated with cocaine addiction in adulthood. Abstinence of cocaine abuse can cause psychiatric symptoms, such as anxiety, psychosis, depression, and cognitive impairments.

Role of phosphodiesterase-4 on ethanol elicited locomotion and narcosis.

The cAMP signaling pathway has emerged as an important modulator of the pharmacological effects of ethanol. In this respect, the cAMP-dependent protein kinase has been shown to play an important role in the modulation of several ethanol-induced behavioral actions. Cellular levels of cAMP are maintained by the activity of adenylyl cyclases and phosphodiesterases.

Role of CA2+/calmodulin on ethanol neurobehavioral effects.

Rationale: The cAMP-dependent protein kinase A (PKA) signaling transduction pathway has been shown to play an important role in the modulation of several ethanol-induced behaviors. Different studies have demonstrated intracellular calcium (Ca(2+))-dependent activation of the PKA cascade after ethanol administration. Thus, the cAMP cascade mediator Ca(2+)-dependent calmodulin (CaM) has been strongly implicated in the central effects of ethanol.

In vivo study of ethanol-activated brain protein kinase A: manipulations of Ca2+ distribution and flux.

Background: The cAMP-dependent protein kinase (PKA) signaling transduction pathway has been shown to play an important role in the modulation of several ethanol (EtOH)-induced behavioral actions. In vivo, short-term exposure to EtOH up-regulates the cAMP-signaling cascade. Interestingly, different Ca(2+) -dependent cAMP-PKA cascade mediators play a critical role in the neurobehavioral response to EtOH, being of special relevance to the Ca(2+) -dependent adenylyl cyclases 1 and 8.

Reduction in central H2O2 levels prevents voluntary ethanol intake in mice: a role for the brain catalase-H2O2 system in alcohol binge drinking.

Background: Hydrogen peroxide (H2 O2 ) is the cosubstrate used by the enzyme catalase to form Compound I (the catalase-H2 O2 system), which is the major pathway for the conversion of ethanol (EtOH) into acetaldehyde in the brain. This centrally formed acetaldehyde has been shown to be involved in some of the psychopharmacological effects induced by EtOH in rodents, including voluntary alcohol intake. It has been observed that different levels of this enzyme in the central nervous system (CNS) result in variations in the amount of EtOH consumed.

Modulation of ethanol-induced conditioned place preference in mice by 3-amino-1,2,4-triazole and D-penicillamine depends on ethanol dose and number of conditioning trials.

Previous studies have shown that both 3-amino-1,2,4-triazole (AT), which inhibits metabolism of ethanol (EtOH) to acetaldehyde by inhibiting catalase, and D-penicillamine (D-P), an acetaldehyde-sequestering agent, modulate EtOH-conditioned place preference (CPP) in male albino Swiss (IOPS Orl) mice. These studies followed a reference-dose-like procedure, which involves comparing cues that have both been paired with EtOH. However, the role of EtOH-derived acetaldehyde has not been examined using a standard CPP method, and efficacy of these treatments could be different under the two circumstances.

The H2O2 scavenger ebselen decreases ethanol-induced locomotor stimulation in mice.

Background: In the brain, the enzyme catalase by reacting with H(2)O(2) forms Compound I (catalase-H(2)O(2) system), which is the main system of central ethanol metabolism to acetaldehyde. Previous research has demonstrated that acetaldehyde derived from central-ethanol metabolism mediates some of the psychopharmacological effects produced by ethanol. Manipulations that modulate central catalase activity or sequester acetaldehyde after ethanol administration modify the stimulant effects induced by ethanol in mice.

α-Lipoic acid, a scavenging agent for H₂O₂, reduces ethanol-stimulated locomotion in mice.

Rationale: The main system of central ethanol oxidation is mediated by the enzyme catalase. By reacting with H(2)O(2), brain catalase forms compound I (the catalase-H(2)O(2) system), which is able to oxidize ethanol to acetaldehyde in the brain. Previous studies have demonstrated that pharmacological manipulations of brain catalase activity modulate the stimulant effects of ethanol in mice.